183182-07-2

Usage

Uses

Used in Pharmaceutical Industry:
(R)-3-Amino-2-benzylpropanoic acid is used as a chiral building block for the synthesis of various pharmaceutical compounds. Its unique structure and chirality make it a valuable component in the development of new drugs with improved efficacy and selectivity.
Used in Drug Development:
(R)-3-Amino-2-benzylpropanoic acid is utilized as a potential molecule for drug development, particularly in the area of opioid receptor agonism. Its structural and pharmacological properties have made it a promising candidate for the treatment of pain and other conditions that may benefit from opioid receptor modulation.
Used in Organic Synthesis:
In the field of organic synthesis, (R)-3-amino-2-benzylpropanoic acid serves as a versatile intermediate for the preparation of a wide range of organic compounds. Its reactivity and the presence of the benzyl group allow for various chemical transformations, making it a useful tool for the synthesis of complex molecules and pharmaceutical agents.

Upstream product

• 197902-88-8 (R)-2-(Benzyloxyamino-methyl)-3-phenyl-propionic acid 
• 18020-59-2 methyl 3-hydroxy-2-methylidene-3-phenylpropionate 
• 100-52-7 benzaldehyde 
• 3695-84-9 methyl benzylidenecyanoacetate 
• 103669-71-2 (Z)-methyl 2-(bromomethyl)-3-phenylacrylate 
• 123802-80-2 (R)-2-hydroxymethyl-3-phenylpropionic acid 
• 123803-51-0 2R-benzyl-3-benzyloxypropanoic acid 
• 501330-98-9 (4R)-4-benzyl-2-[(1S)-1-phenylethyl]isoxazolidin-5-one 
• 132696-47-0 (R)-2-(benzyloxycarbonylaminomethyl)-3-phenylpropanoic acid 
• 183182-00-5 1-benzoyl-(2S)-tert-butyl-3-methyl-(5R)-benzylperhydropyrimidin-4-one 
• 916322-65-1 (R)-β-azido-α-benzylpropanoic acid 
• 501-52-0 3-Phenylpropionic acid 
• 34880-68-7 2,2,6,6-tetramethyl-4-(2-phenylethylidene)-3,5-dioxa-2,6-disilaheptane 
• 104-52-9 phenylpropyl chloride 

Downstream Products

• 828254-16-6 (2R)-2-benzyl-3-(9H-fluoren-9-ylmethoxycarbonylamino)propionic acid 
• 26250-90-8 (R)-3-tert-butyloxycarbonyl-β²-homophenylalanine 

Relevant academic research and scientific papers

Catalytic Asymmetric Synthesis of Unprotected β2-Amino Acids

We report here a scalable, catalytic one-pot approach to enantiopure and unmodified β2-amino acids. A newly developed confined imidodiphosphorimidate (IDPi) catalyzes a broadly applicable reaction of diverse bis-silyl ketene acetals with a silylated aminomethyl ether, followed by hydrolytic workup, to give free β2-amino acids in high yields, purity, and enantioselectivity. Importantly, both aromatic and aliphatic β2-amino acids can be obtained using this method. Mechanistic studies are consistent with the aminomethylation to proceed via silylium-based asymmetric counteranion-directed catalysis (Si-ACDC) and a transition state to explain the enantioselectivity is suggested on the basis of density functional theory calculation.

β2-Homo-amino acid scan of μ-selective opioid tetrapeptide TAPP

TAPP (H-Tyr-d-Ala-Phe-Phe-NH2) is a potent, μ-selective opioid ligand. In order to gain further insights into pharmacophoric features of this tetrapeptide, we have performed a β2-Homo-amino acid (β2hAA) scan of the TAPP sequence. To this aim, 10 novel analogues have been synthesized and evaluated for μ-opioid and δ-opioid receptor affinity as well as for stability in human plasma. The derivatives included compounds in which a (R)- or (S)-β2-Homo-Homologue replaced the amino acids in the TAPP sequence. The derivatives with (R)- or (S)-β2hPhe4 turned out to bind μOR with affinities equal to that of the parent. β2hAAs in position 1 and 3 resulted in rather large affinity decreases, but the change differed depending on the stereochemistry. β2-Homologation in the second position gave derivatives with very poor μOR binding. According to molecular modelling, the presented α/β-peptides adopt a variety of binding poses with their common element being an ionic interaction between a protonable amine of the first residue and Asp147. A feature required for high μOR affinity seems the ability to accommodate the ring in the fourth residue in a manner similar to that found for TAPP. Contrary to what might be expected, several compounds were significantly less stable in human plasma than the parent compound.

Trans-hexahydrobenzoxazolidinones in the enantioselective synthesis of β2-amino acids containing proteinogenic side chains

The use of enantiopure trans-hexahydrobenzoxazolidinones as chiral auxiliaries in the enantioselective synthesis of two β2-amino acids containing proteinogenic side chains (β2-hPhenylalanine and β2-hLysine), in both enantiomeric forms, is described. Absolute configurations were assigned on the basis of X-ray diffraction analysis and chemical correlation methods.

A general approach to the synthesis of β2-amino acid derivatives via highly efficient catalytic asymmetric hydrogenation of α-aminomethylacrylates

A new strategy was developed for the synthesis of a valuable class of α-aminomethylacrylates via the Baylis-Hillman reaction of different aldehydes with methyl acrylate followed by acetylation of the resulting allylic alcohols and SN2′-type amination of the allylic acetates. Asymmetric hydrogenation of these diverse olefinic precursors using rhodium(Et-Duphos) catalysts provided the corresponding β2-amino acid derivatives with excellent enantioselectivities and exceedingly high reactivities (up to >99.5% ee and S/C=10,000). The first hydrogenation of (Z)-configurated substrates was studied for the synthesis of β2-amino acid derivatives. The high influence of the substrate geometry and steric hindrance on the reactivity and enantioselectivity was also disclosed for this reaction. This protocol provides a highly practical, facile and scalable method for the preparation of optically pure β2- amino acids and their derivatives under mild reaction conditions.

β-aminopeptidase-catalyzed biotransformations of β2- dipeptides: Kinetic resolution and enzymatic coupling

We have previously shown that the β-aminopeptidases BapA from Sphingosinicella xenopeptidilytica and DmpA from Ochrobactrum anthropi can catalyze reactions with non-natural β3-peptides and β3-amino acid amides. Here we report that these exceptional enzymes are also able to utilize synthetic dipeptides with N-terminal β2-amino acid residues as substrates under aqueous conditions. The suitability of a β2-peptide as a substrate for BapA or DmpA was strongly dependent on the size of the Cα substituent of the N-terminal β2-amino acid. BapA was shown to convert a diastereomeric mixture of the β2-peptide H-β2hPhe- β2hAla-OH, but did not act on diastereomerically pure β2,β3-dipeptides containing an N-terminal β2-homoalanine. In contrast, DmpA was only active with the latter dipeptides as substrates. BapA-catalyzed transformation of the diastereomeric mixture of H-β2hPhe-β2hAla-OH proceeded along two highly S-enantioselective reaction routes, one leading to substrate hydrolysis and the other to the synthesis of coupling products. The synthetic route predominated even at neutral pH. A rise in pH of three log units shifted the synthesis-to-hydrolysis ratio (vS/vH) further towards peptide formation. Because the equilibrium of the reaction lies on the side of hydrolysis, prolonged incubation resulted in the cleavage of all peptides that carried an N-terminal β-amino acid of S configuration. After completion of the enzymatic reaction, only the S enantiomer of β2-homophenylalanine was detected (ee>99% for H-(S)-β2-hPhe-OH, E>500); this confirmed the high enantioselectivity of the reaction. Our findings suggest interesting new applications of the enzymes BapA and DmpA for the production of enantiopure β2-amino acids and the enantioselective coupling of N-terminal β2-amino acids to peptides.

Highly diastereoselective synthetic route to enantiopure β2-amino acids and γ-amino alcohols using a fluorinated oxazolidine (Fox) as chiral auxiliary

(Chemical Equation Presented) The alkylation reactions of an amide enolate derived from a trifluoromethylated oxazolidine (Fox) chiral auxiliary occur with a complete diastereoselectivity and in good yields with various electrophiles. This reaction provid

Rhodium-catalyzed enantioselective hydrogenation of β-phthalimide acrylates to synthesis of β2-amino acids

The enantioselective hydrogenation of β-phthalimide acrylates provides the corresponding chiral β2-amino acids in excellent enantiomeric excess catalyzed by Rh-monophosphorus.

Nitrile biotransformations for the practical synthesis of highly enantiopure azido carboxylic acids and amides, 'click' to functionalized chiral triazoles and chiral β-amino acids

Under very mild conditions, biotransformations of racemic azido nitriles using Rhodococcus erythropolis AJ270, a nitrile hydratase/amidase-containing microbial whole-cell catalyst, afforded highly enantiopure, (R)-α-arylmethyl- and (+)-α-cyclohexylmethyl-β-azidopropanoic acids and their (S)- and (-)-carboxamide derivatives in excellent yields. The resulting functionalized chiral organoazides were converted in a straightforward fashion to a pair of antipodes of α-benzyl-β-amino acids (R)-13 and (S)-13. Azido carboxamide (S)-11a and azido carboxylic acid (R)-12a underwent 'click' reactions with diethyl acetylenedicarboxylate and phenylacetylene to produce functionalized chiral triazoles 14 and 15, respectively. The easy preparation of the starting nitrile substrates, highly efficient and enantioselective biotransformation reactions, and versatile utility of the resulting functionalized azido carboxylic acids and amide derivatives, render this method very attractive and practical in organic synthesis.

Application of Oppolzer's sultam in the synthesis of cyclic α-amino acids and β-amino acids

In this paper we describe the application of Oppolzer's sultam as a chiral auxiliary for the synthesis of cyclic α- and β2-amino acids. The key step of the synthesis is stereoselective alkylation of sultam-derived glycine and β-alanine Schiffs bases leading to diastereometrically pure products. Final compounds are obtained after mild acidic and next basic hydrolyses of auxiliary groups and can be directly converted into N-tert-butoxycarbonyl- or N-fluorenylmethoxycarbonyl derivatives useful in peptide synthesis. In the case of substrates alkylated with dihalogenoalkanes spontaneous cyclization occurring during removal of the auxiliary groups yields cyclic α-amino acids (proline homologues) with reasonable yield and stereoselectivity. Theoretical data explain the differences in tendency for cyclization between α- and β-amino acids.

Efficient synthesis of enantiomerically pure β2-amino acids via chiral isoxazolidinones

We report a practical and scalable synthetic route for the preparation of α-substituted β-amino acids (β2-amino acids). Michael addition of a chiral hydroxylamine, derived from α-methylbenzylamine, to an α-alkylacrylate followed by cyclization gives a diastereomeric mixture of α-substituted isoxazolidinones. These diastereomers are separable by column chromatography. Subsequent hydrogenation of the purified isoxazolidinones followed by Fmoc protection affords enantiomerically pure Fmoc-β2-amino acids, which are useful for β-peptide synthesis. This route provides access to both enantiomers of a protected β2-amino acid.